Cytopathology provides definitive diagnoses that direct patient management and treatment. The Cytopathology Section provides complete diagnostic service in cytopathology for the various clinical protocols of the NIH. We specialize in the application of ancillary diagnostic techniques (i.e., immunocytochemistry, flow cytometry, and, most recently, molecular diagnostics) to patient material for the confirmation of morphologic diagnoses and collaborative investigations. The Cytopathology Section has a distribution of specimens as follows: fine needle aspiration (FNA), 30 percent; central nervous system (CNS), 33 percent; effusions, 8 percent; respiratory, 9 percent; genitourinary (GU), 10 percent; cervical/vaginal, 7 percent; gastrointestinal (GI), 1 percent; miscellaneous, 2 percent. The section has a high rate of malignancy--25 percent of all accessioned specimens. Due to the nature of the specimen material, a large number of our cases require immunoperoxidase studies (20 percent). The immunosuppressed nature of the patient population dictates that a significant proportion of our cases require special studies for pathologic organisms (10 percent). The relatively high rate of pathologic findings combined with the diversity of types of exfoliative and FNA specimens provide a broad experience in diagnostic cytopathology for residency and fellowship training. The Cytopathology Section is involved in numerous clinically related research projects, many of which utilize FNA with immunocytochemistry and molecular techniques to provide ancillary diagnostic information. A partial listing of such studies includes: (1) evaluation, quantitation, and monitoring of expression of malignant melanoma antigens (MART-1, gp100, tyrosinase) and HLA antigens through the utilization of monoclonal antibodies in FNAs from malignant melanoma patients prior to and during treatment with vaccine therapy; (2) evaluation and quantitation of subsets of T cells during immunotherapy for malignant melanoma; (3) evaluation of FNA material for subsequent polymerase chain reaction (PCR), microarray, and proteomics technologies; (4) evaluation of numerous protocol-driven neoplasms for possible immunotherapy; and (5) evaluation of breast ductal lavage samples from high-risk populations for morphology and eventual biomarkers.